Fig 1: A working model shows that YTHDF1 and YTHDF2 work synergistically to regulate Wnt5a-PCP signaling pathway and cerebellar granule cell axon growth. A) Under normal conditions, YTHDF1 promotes the translation of m6A-modified Dvl1 mRNA in GC axons. Dvl1 can block Wnt5a-Fzd3-activated PCP signaling. Meanwhile, YTHDF2 facilitates Wnt5a mRNA degradation to downregulate Wnt5a protein level in GC axons. So both YTHDF1 and YTHDF2 negatively regulate Wnt5a-PCP signaling pathway and GC axon growth. B) In Ythdf1 and Ythdf2 cKO mice, local translation of Dvl1 mRNA and decay of Wnt5a mRNA in GC axons are inhibited, respectively. The resulting downregulation of Dvl1 and upregulation of Wnt5a protein levels in axons potentiate Wnt5a-PCP signaling and promote GC axon growth.